PUBLICATION
The Calmodulin-Stimulated Adenylate Cyclase ADCY8 Sets the Sensitivity of Zebrafish Retinal Axons to Midline Repellents and Is Required for Normal Midline Crossing
- Authors
- Xu, H., Leinwand, S.G., Dell, A.L., Fried-Cassorla, E., and Raper, J.A.
- ID
- ZDB-PUB-100601-16
- Date
- 2010
- Source
- The Journal of neuroscience : the official journal of the Society for Neuroscience 30(21): 7423-7433 (Journal)
- Registered Authors
- Raper, Jonathan
- Keywords
- none
- MeSH Terms
-
- Embryo, Nonmammalian
- Nerve Tissue Proteins/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Adenylyl Cyclases/genetics
- PubMed
- 20505109 Full text @ J. Neurosci.
Abstract
The chemokine SDF1 activates a cAMP-mediated signaling pathway that antagonizes retinal responses to the midline repellent slit. We show that knocking down the calmodulin-activated adenylate cyclase ADCY8 makes retinal axons insensitive to SDF1. Experiments in vivo using male and female zebrafish (Danio rerio) confirm a mutual antagonism between slit signaling and ADCY8-mediated signaling. Unexpectedly, knockdown of ADCY8 or another calmodulin-activated cyclase, ADCY1, induces ipsilateral misprojections of retinal axons that would normally cross the ventral midline. We demonstrate a cell-autonomous requirement for ADCY8 in retinal neurons for normal midline crossing. These findings are the first to show that ADCY8 is required for axonal pathfinding before axons reach their targets. They support a model in which ADCY8 is an essential component of a signaling pathway that opposes repellent signaling. Finally, they demonstrate that ADCY8 helps regulate retinal sensitivity to midline guidance cues.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping